Exercise Changes DNA for the Better, New Study Finds

By Editor, on March 8th, 2012

A new study has found that even 20 minutes of exercise by sedentary adults actually changed the DNA in their muscle cells within minutes. The DNA was changed in a way that helps the muscles work better for further exercise, and also turns on certain genes that are active in good metabolism of sugar and fat and in glucose regulation. This could in turn help counteract the onset of diabetes.

The new study illuminated the mechanism through which muscle contraction produced by exercise may remove chemicals called “methyl groups” from certain points on the DNA. Removing the “methyl groups” means removing barriers that otherwise limit the cell’s ability to access or switch on certain genes that are active in metabolism and involved in muscle oxidation and glucose regulation.

These positive effects upon the DNA increased as the intensity of exercise increased, the researchers found.

“Exercise is medicine, and it seems the means to alter our epigenomes [genes] for better health may be only a jog away,” said Juleen Zierath, the principal author of the new study, who is a Professor of Clinical Integrative Physiology at the Department of Molecular Medicine and Surgery at the Karolinska Institute in Stockholm, Sweden.

The Study; Methodology

The researchers included in their study a group of 14 young men and women who were relatively sedentary. As part of the study, these volunteer participants worked out for periods of approximately 20 minutes on an exercise bicycle that measured their maximum activity levels.

The participants exercised at two different intensities over a period of a week. On one visit, they cycled until they reached 40% of their maximum capacity. On a second visit, they cycled until they reached 80% of their maximum capacity.

The participants also volunteered to have a biopsy procedure performed under local anesthesia on a small piece of muscle from their quadriceps (thigh muscle). On each exercise visit, the researchers took the biopsy of muscle cells once before the participants exercised, and again within 20 minutes after exercise.

Using the biopsied muscle samples, the researchers analyzed and compared the state of the DNA in the muscle tissue and the activity level of certain muscle-related genes, before and after exercise.

Findings

The researchers found greater concentrations of chemicals called “methyl groups” at certain points on the DNA before exercise, and lesser concentrations of methyl groups after exercise.

The authors explained that the presence of methyl groups limits the cell’s ability to access or switch on certain genes within the DNA. Through controlling the concentration or removal of these methyl groups at points on the DNA (a molecular process called “methylation”), the body regulates which genes in the DNA are activated. “Those changes [the concentration or removal of the methyl groups] occur in stretches of DNA that serve as landing sites for different kinds of enzymes, called transcription factors, which in turn are involved in turning ‘on’ genes already known to be important in muscles’ adaptation to exercise,” as well as in metabolism of sugar and fat, the Karolinska Institute explained in a release about the new study.

In analyzing the biopsied muscle tissue of the study participants before and after each episode of exercise, the researchers discovered that within 20 minutes after exercise, the participants’ DNA showed less methylation (presence of less methyl groups). This suggests that the muscle contraction of exercise serves to diminish the methyl groups in the DNA, thereby unblocking and activating certain genes.

Indeed, after exercise, the researchers found greater concentrations of three genetic transcription factors, PGC-1α, PDK4, and PPAR-δ, among others, that are known to play a role in muscle adaptation to exercise and in metabolism, and specifically in the regulation of glucose in the system.

The more intense the exercise, the less the concentration of methyl groups and the more such gene activity, the researchers found after exercise.

The researchers explained that the process of methylation and activation of the referenced genetic transcription factors, not only helps metabolism, but also helps to prepare muscle cells for further exercise, activating them to release the right enzymes and nutrients that the muscle will need to burn calories and get energy while the person continues exercising.

“We are trying to get at the early messages that the muscle is [receiving in order] to say, ‘Something is happening here, we need to coordinate so we can get more enzymes and more machinery on board so we can cope with the demands of this exercise,” Professor Zierath, the principal study author, explained to Time.

The studied genes in fact perform a variety of metabolic functions. “PGC-1α is a transcription factor that increases the oxidation of muscle, TFAM regulates the transcription of mitochondrial DNA, and MEF2A regulates the transport of glucose in and out of cells,” as reported by The Scientist. “All of these genes have been previously shown to be involved with exercise,” Charlotte Ling, an epigenetics research at Lund University, who did not take part in the study, told The Scientist. “And they’re also connected to diabetes,” she said.

The Karolinska researchers also performed a series of related experiments on rat leg muscle tissue in order to illuminate the cellular mechanism through which the muscle contraction of exercise acts to decrease methylation and unblock and activate the referenced genes.

They found that a release of calcium by muscle cells upon contraction plays a role in the process. When muscle cells contract upon start-up of exercise, they release calcium, which in turn fuels the contraction process and the removal of methyl groups and activation of the referenced genes, the researchers explained.

They tested this in the rat muscle cells, first by blocking calcium production by those cells. When they did this, as expected, they found that the muscles failed to contract to the same extent as when the cells are allowed to release calcium normally upon contraction, and this slowed the removal of methylation.

The researchers than administered a high dose of caffeine to the rat muscle cells. The caffeine, which is known to trigger the release of calcium from cells, indeed did enhance the removal of methyl groups and activation of the genes that help muscles contract — an effect similar to that seen after exercise.

Professor Zierath, however, cautions that this does not mean that coffee can be substituted for exercise. “Most of the physiological effect of the caffeine we drink is on the central nervous system, and not dispersed to all the muscles,” she said. “In order to get the same kind of effect we saw in the [rats'] cells, you would have to drink 50 cups of coffee a day, which is close to the lethal dose. In my mind, half an hour of moderately high intensity exercise is sufficient to do the same thing.”

Conclusions and Implications

In a scientific summary of their findings, the researchers wrote: “Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation [reduction in methyl groups on the DNA] is an early event in contraction-induced gene activation [through exercise].”

In a press release, the Karolinska Institute said their new study showed that, “when healthy but inactive men and women are made to exercise it actually alters their DNA – in a matter of minutes.” “Those so called epigenetic modifications to the DNA, at precise locations, appear to be an important part of the physiological benefits of exercise.”

“We often say ‘You are what you eat.’ Well, muscle adapts to what you do. If you don’t use it, you lose it and this is one of the mechanisms that allow that to happen,” said Professor Juleen Zierath, the principal study author.

“Exercise is already known to induce changes in muscle, including increased metabolism of sugar and fat”, Professor Zierath said. “Our discovery is that the methylation change comes first,” she explained.

In an earlier study in 2009, Professor Zierath had shown that diabetics have different DNA methylation patterns in muscle than those without diabetes, making it more difficult for them to regulate insulin properly. Having now shown the mechanism through which exercise can actually affect methylation and induce the genetic activity lacking in diabetics but needed for regulation of insulin, she told The Scientist, “Exercise is one therapeutic to maintain sensitivity of the organs to insulin and prevent diabetes.”

“Exercise is medicine, and it seems [that] the means to alter our epigenomes [genes] for better health may be only a jog away,” Professor Zierath concluded.

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